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Clin Pediatr Endocrinol. 2018;27(3):179-186. doi: 10.1297/cpe.27.179. Epub 2018 Jul 31.

A case of perinatal hypophosphatasia with a novel mutation in the ALPL gene: clinical course and review of the literature.

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Department of Pediatrics, Osaka Hospital, Japan Community Healthcare Organization (JCHO), Osaka, Japan.
Department of Pediatrics and Neonatology, Takatsuki General Hospital, Osaka, Japan.
Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Department of Bone and Mineral Research, Research Institute of Osaka Women's and Children's Hospital, Osaka, Japan.


Hypophosphatasia (HPP) is a metabolic bone disease characterized by failure of bone calcification and vitamin B6 dependent seizures. It is caused by loss-of-function mutations in the ALPL gene. A newborn girl required respiratory support by nasal-directional positive airway pressure at birth, and pyridoxine hydrochloride administration for vitamin B6-dependent seizures observed from day two. Umbilical cord blood showed low alkaline phosphatase (ALP) activity and high pyridoxal phosphate levels. Radiographs showed severe rickets-like appearance of the bones. Genetic analysis of the ALPL gene revealed compound heterozygous mutations, c.1559delT/p.Ser188Pro. We diagnosed her with perinatal severe HPP, and started the patient on asfotase alfa from day six. Following enzyme replacement therapy (ERT), skeletal mineralization and respiratory insufficiency improved with no remarkable side-effects. Crying vital capacity (CVC) was used to evaluate respiratory status, which continuously improved from 13.3 mL/kg (day 22) to 20.6 mL/kg (day 113). Since no seizures occurred, pyridoxine hydrochloride was tapered off at one year of age. Strategies to manage perinatal severe HPP cases following ERT have not been established till date. A review of the literature shows that CVC may be a good indicator for weaning from ventilatory support. In addition, ERT will most likely enable withdrawal of pyridoxine treatment.


ALPL; asfotase alfa; crying vital capacity; pyridoxal phosphate; pyridoxine hydrochloride

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